We propose to develop an innovative prototype imaging system which combines the unique properties of the Compact Light Source (a new x-ray source developed with NIGMS SBIR funding) with a new imaging method called Differential Phase Contrast Imaging. This Clinical High Resolution Imaging System (CHRIS) will yield x-ray images which can distinguish subtle variations in soft tissue at an extremely fine scale. The Compact Light Source (CLS), developed with a grant from the Protein Structure Initiative of the NIGMS, is a high-intensity, tunable synchrotron light source that is small enough for clinical implementation. DPCI is an elegant new imaging technology that has demonstrated superior visualization of soft tissue using x-rays. Image contrast for DPCI is caused by the phase shift of x-rays passing through the subject and therefore does not rely upon absorption as with conventional x-ray techniques. The DPCI technique provides three improved contrast mechanisms to reveal specific soft tissue detail not revealed in standard radiographs: higher-quality absorption contrast arising from the nearly monochromatic point-like x-ray source;phase contrast that highlights the density variation of soft tissue;and dark-field contrast which accentuates small-angle scattering from the fine structure of soft tissue. DPCI, as a transmissive technique, also favors high-energy x-rays (30 keV or higher) that can significantly reduce the absorbed dose received by the patient over conventional x-ray techniques. CHRIS is intended to integrate these two innovative technologies-the CLS and DPCI-to produce a turnkey system for both 2-D and tomographic imaging of phantoms and tissue samples with all of the degrees of freedom necessary to simulate the motions required for clinical applications;it will be implemented with the intent of later handling patients without significant re-engineering. When complete, the CHRIS will be a product which will enable the development of clinical applications of this new method towards cancer detection, mammography, osteoarthritis, small animal imaging and other clinical radiological applications which require the detection of fine structure within soft tissue. The CHRIS proposal seeks to develop a new, versatile state-of-the-art instrument to enable both basic biomedical research and clinical investigations of a wide range of health issues. PUBLIC HEALTH RELEVANCE: The proposed Clinical High Resolution Imaging System (CHRIS) will extend the power of present x-ray diagnostic imaging by employing new contrast mechanisms to show extremely fine details within soft tissue that conventional radiography cannot reveal. This improved x-ray imaging would enable researchers to better understand disease and therapies and help to diagnose and treat disease at the earliest detectable stage. CHRIS will be a new state-of-the-art instrument to enable both basic biomedical research and clinical investigations of a wide range of health issues, including the early detection of cancer, in vivo imaging of small animals, as well as other soft tissue applications.